As dosage form for orally administered medicines, a capsule formulation comprising a capsule shell and a material encapsulated in the capsule (encapsulated material) is widely used. The most frequently used capsule shell base for forming a capsule shell is gelatin. However, a formulation produced with a capsule shell comprising gelatin as a capsule shell base (gelatin capsule shell) may cause delay in dissolution of a drug out of the capsule shell because an encapsulated material may interact with gelatin during storage.
Orally administered medicines are ingested and then allow dissolution of a drug from a formulation and the drug is then absorbed through the gastrointestinal tract to exhibit the pharmacological effects. Therefore, a formulation which has delayed dissolution due to storage generally shows decreased absorption of a drug through the gastrointestinal tract and does not provide sufficient pharmacological effects.
As a compound which generally interacts with gelatin, a compound having a carbonyl group or an aldehyde group, reducing sugars and a compound which produces aldehyde during storage are known. Specific examples thereof include lactose and polyethylene glycol (macrogol).
However, dissolution may not always be delayed to such an extent that the pharmacological effects of medicines are affected even when a compound interacting with gelatin is encapsulated in a gelatin capsule shell. For example, medicines which comprise granules comprising lactose or polyethylene glycol encapsulated in a gelatin capsule shell are widely distributed. In addition, a gelatin capsule shell comprising polyethylene glycol in the capsule shell per se is also commercially available and medicines using the capsule shell are also distributed in Japan.
Thus it is difficult to predict whether or not a medicine comprising a drug encapsulated in a gelatin capsule shell causes delay in dissolution to such an extent that the pharmacological effects may be affected.
Ravuconazole is a triazole compound having an anti-fungal effect and has low water solubility. Patent Document 1 discloses a phosphonooxymethyl derivative of ravuconazole which is a prodrug of ravuconazole having improved solubility. Patent Document 2 discloses a formulation comprising a phosphonooxymethyl derivative of ravuconazole. However, Patent Document 2 does not disclose dissolution behavior of the phosphonooxymethyl derivative of ravuconazole from the formulation or delay in dissolution due to storage and does not disclose the capsule shell base.